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However, logistical challenges in magnetic resonance imaging (MRI) limit its application, hindering the understanding of CPT's neural dynamics. To address this, we acquired resting\u2010state functional MRI (fMRI) data from 30 healthy participants before, during and after immersion in gelled\u2010cold water, the closest in\u2010scanner alternative to date to CPT for prolonged stimulation. Participants provided subjective pain intensity ratings after each scan, as well as average pain perceived during noxious stimulation, using a numeric rating scale (NRS). Following fMRI, participants rated their pain continuously during identical tonic noxious stimulation of the contralateral hand using a visual analogue scale (VAS). We employed three complementary methods to examine changes in brain function across fMRI conditions: a data\u2010driven approach via independent component analysis (ICA), seed\u2010to\u2010whole\u2010brain connectivity analysis with the periaqueductal grey (PAG) as seed and spectral dynamic causal modelling (spDCM) to explore effective connectivity changes across the dorsal anterior cingulate cortex (dACC), anterior insulae (AI), thalamus and PAG. NRS scores were significantly higher following tonic cold compared to baseline and recovery conditions. Continuous VAS reflected sustained mild\u2010to\u2010moderate pain over 6\u2009min, with average VAS scores not significantly differing from NRS ratings recorded in the scanner. ICA identified engagement of descending pain control and sensorimotor networks during pain, with the latter persisting during recovery. Seed\u2010based analysis revealed a disengagement between the PAG and cortical\/subcortical regions involved in pain processing, such as the dACC, midcingulate cortex, AI, intraparietal sulcus and precuneus. Finally, spDCM revealed tonic pain neural signature was most likely characterised by top\u2010down inhibitory and bottom\u2010up excitatory connections. This study establishes the cold gelled\u2010water paradigm as a potential in\u2010scanner alternative to CPT. By uncovering key neural dynamics of CPT, we provide new insights into the brain and brainstem mechanisms of tonic cold pain paradigms routinely used in psychophysical pain studies.<\/jats:p>","DOI":"10.1002\/hbm.70291","type":"journal-article","created":{"date-parts":[[2025,7,25]],"date-time":"2025-07-25T11:14:33Z","timestamp":1753442073000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["A Novel Investigation of an In\u2010Scanner Alternative to the Cold Pressor Test in Healthy Individuals"],"prefix":"10.1002","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8883-6520","authenticated-orcid":false,"given":"Sonia","family":"Medina","sequence":"first","affiliation":[{"name":"Department of Clinical and Biomedical Sciences, Health and Life Sciences University of Exeter  Exeter UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sam 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